For the first time, researchers have been able to successfully report the structure of a Class B G-Protein Coupled Receptor (GPCR) using lipidic cubic phase (LCP) protein crystallisation.

The work performed at Heptares, a leading drug discovery and development company,
and published this week in Nature, details the structural identification of the stress receptor, corticotropin-releasing factor receptor 1 (CRF1). This pioneering discovery opens up the technique to an entirely new group of molecules with important roles in the development of diseases as diverse as diabetes, osteoporosis, depression and anxiety.

The mosquito® LCP, an innovative solution for LCP crystallography designed by TTP Labtech, was a significant technical driving force enabling the research and underlines the company’s role in facilitating cutting-edge drug discovery research.

Dr. Andrew S. Doré, Head of Crystallography at Heptares Therapeutics Ltd and co-author of the recent article in Nature, said: “In any crystallographic project, eliminating variables is key in producing a steady stream of crystallisation grade protein for structure determination efforts. This of course also extends to crystallisation itself.” He continued: “We had to stitch together data from 35 isomorphous crystals to produce a full dataset for the CRF1 structure solution. mosquito LCP provided a reliable platform for our CRF1 LCP crystallisation, deploying reproducible low volume boli at speed, and ultimately yielding a large sample set of CRF1 crystals for subsequent diffraction analysis.”

“We’ve worked closely with Dr Doré’s team at Heptares since 2010 – in fact they were one of the earliest adopters of the mosquito LCP,” said Joby Jenkins, Global Director of Automation at TTP Labtech. “Heptares has now solved in excess of 35 GPCR structures to date – no mean feat when working with such a complex experimental process. We are delighted to have the opportunity to work with such a talented team and look forward to the new GPCR discoveries in the future.”